• Biomolecules & Therapeutics
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• 제4권3호
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• pp.265-270
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• 1996

The purpose of this study was to determine pharmacokinetic parameters and tissue distribution patters of urinary trypsin inhibitor(UTI) in Sprague-Dawley rats. $Na^{125}$I was conjugated to UTI to make $^{125}I-UTI$ and the concentrations were determined by $\gamma$-counter. With the aid of nonlinear least-square regression analysis for i.v bolus injection of 1,000 unit UTI including $^{125}I-UTI$, the temporal concentration curves were best fitted by 2-compartment open model. The distribution phase half-life was 0.39$\pm$0.02 hours whereas the elimination half-life was 12.99$\pm$1.05 hours in male rats. The volume of distribution and total body clearance in male rats were 0.28$\pm$0.01 1/kg and 83.16$\pm$1.15 ml/kg/h, respectively. We could not find any difference of pharmacokinetic parameters of UTI between male and female rats. UTI were distributed widely in rat organs. In both male and female rats, the kidney was the highest distributed organ. Amount of UTI in 24 hour cumulative urine in male rats was 36.22$\pm$8.74% and that in 48 hours was 43.32$\pm$10.55%. Excretion via feces was very scanty, with the 24 hours cumulative amount being only 2.76$\pm$0.97%. This data suggest the main excretion route of UTI is urine.

• 한방비만학회지
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• 제18권1호
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• pp.36-49
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• 2018

Objectives: The study is aimed at evaluating the possible toxicity in 90-day repeated oral administration of modified Samjung-hwan (mSJH) in Sprague-Dawley (SD) rats. This study was conducted to detect the no-observed adverse effect level (NOAEL). Methods: Modified SJH extract was administered orally in male and female SD rats at dose of 0, 1,000, 2,000, 4,000 mg/kg. Each group consisted of 10 rats of each gender. The modified SJH extract was given once a day for 90 days. We monitored the changes of mortalities, clinical signs, body weight changes, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers of all animals treated with modified SJH extract during the study period. Results: There were no toxicologically significant changes in mortalities, clinical signs, body weight gains, food consumption, ophthalmologic findings, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histological markers in any of rats tested. Conclusions: The NOAEL of the modified SJH extract in male rats and no observed effect level (NOEL) in female rats are considered 4,000 mg/kg.

• Toxicological Research
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• 제35권1호
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• pp.65-74
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• 2019

Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.

• Biomolecules & Therapeutics
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• 제4권1호
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• pp.19-31
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• 1996

This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.

• 한국산업보건학회지
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• 제21권2호
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• pp.73-81
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• 2011

The purpose of this study was to obtain scientific information regarding classification and health hazards that may result from a 13 weeks inhalation exposure of isoprene in Sprague-Dawley (SD) rats. The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 413. The Rats were divided into 4 groups (10 male and 10 female rats in each group) and exposed to 0, 360, 1,620, 7,300 ppm isoprene in each exposure chamber for 6 h/day, 5 days/week, for 13 weeks. As a result, there were no mortality or abnormality during the period of study and did not show any significant changes of body weight. There were no dose response changes in urinalysis, hematological and serum biochemical value examination. Relative organ weight was increased significantly the right kidney in 7,300 ppm group of male rats. In female rats, relative organ weight of the left kidney and the both lungs in 1,620 ppm group and the left lung and the both kidneys in 7,300 ppm group were increased significantly. But the histopathological findings did not reveal any exposure-related changes. According to the above results, the no observable adverse effect level (NOAEL) of isoprene was 7,300 ppm (20.3 mg/L) in both male and female rats. In conclusion, Isoprene was not classified specific target organ toxicity of the 'Standard for Classification and Labeling of Chemical Substance and Material Safety Data Sheet' (Ministry of Employment and Labor, 2009).

• 한국식품영양과학회지
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• 제12권3호
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• pp.264-272
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• 1983

실험식이의 에너지수준은 저에너지(3,200kcal/kg) 중에너지(3,600kcal/kg), 고에너지(4,000kcal/kg)로 달리했으며, 저단백질(15%), 중단백질(25%), 고단백질(35%)의 3수준으로 하고, 지방수준은 ME 3,600kcal/kg에 대해서 저지방(10%), 중지방(20%), 고지방(40%)의 3수준으로 정하고 나머지 에너지는 전분과 포도당으로 보충한 9종의 식이에 대한 대사실험 결과를 요약하면 다음과 같다. 1. 고형물 조단백질 조지방, 탄수화물의 소화율은 저에너지 수준에서 중 고에너지 수준에서보다 훨씬 낮았으며, 중 고에너지 수준사이에 큰 차이가 없었다. 단백질 수준이 높아질수록 고형물과 탄수화물의 소화율은 약간씩 감소되는 경향이었으며, 단백질의 소화율은 증가되는 경향이었다. 조지방의 소화율은 식이 단백질의 영향을 받지 않았으나 에너지 수준이 높을 때 즉 식이에 포함된 지방함량이 높을 때 증가되었으며 암수 모두 같은 경향을 보였다. 각 영양소의 소화율은 고형물 약 83%, 조단백질 90%, 조지방 96%, 탄수화물 93%로서 단백질과 에너지 수준에 따라 거의 차이가 없었으며 암수 간에는 차이가 없었다. 2. 질소 축적율은 암수 모두 식이 단백질 수준이 증가할수록 감소되는 반면 식이 에너지 수준이 증가할수록 증가되는 것을 볼 수 있었다. 따라서 단백질 수준은 NRC 사양 표준치에서, 에너지 수준은 그 이상에서 암수 모두 질소 축적율이 가장 높았다. 3. 에너지 이용율은 암쥐의 경우 식이 단백질 수준이 증가할수록 감소되었으며 식이 에너지 수준이 증가할수록 증가되었다. 숫쥐의 경우 식이 단백질 수준이 증가함에 따라 감소되었으나, 암쥐와는 달리 중에너지 수준에서 가장 높았다. 즉 단백질 수준은 암수 모두 NRC 사양 표준치에서 에너지 대사율이 가장 높았으나 에너지 수준은 암쥐의 경우 NRC 사양 표준치 이상에서, 숫쥐의 경우 NRC 사양 표준치에서 각각 가장 높았다.

• Journal of Nutrition and Health
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• 제39권4호
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• pp.338-346
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• 2006

The overall purpose of this study was to investigate the effects of level of isoflavones supplementation on bone metabolism in growing female rats. The effects of level of isoflavones supplementation on bone mineral density (BMD) and bone mineral content (BMC) were inspected in this study. Forty-five rats divided into three groups: Casein, $^1/{_2}IF$, IF. The serum and urine concentrations of calcium and phosphorus were determined. BMD and BMC were estimated by using PIXImus (GE Lunar Co, Wisconsin.) in spine and femur on 3, 6, 9 weeks after feeding. This study of results were as follows: The isoflavones supplementation level did not affect weight gain, mean food intake and food efficiency ratio. The serum concentration of calcium, phosphorus were not significantly different by different level of isoflavones supplementation. The urinary calcium and phosphorus excretion were not significantly different, too. Spine and femur BMD, BMC were not significantly increased by different level of isoflavones supplementation on 3 and 6 weeks after feeding. Spine BMD and spine BMC per weight, femur BMC per weight were significantly increased in the groups $^1/{_2}IF$ and IF at the ninth week after feeding, but there was no significant difference by different level of isoflavones supplementation. Spine BMD per weight and femur BMD per weight were significantly higher in the group of IF than in the group of Casein and $^1/{_2}IF$ at the ninth week after feeding. These results suggest that the group of IF with rich isoflavones supplementation was effective to the increase of BMD spine and femur in growing female rats, respectively.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.151-156
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• 2017

High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats.

• Toxicological Research
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• 제8권2호
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• pp.205-216
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• 1992

cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R), an antitumor platinum complex, was selected for clinical evaluation on the basis of its experimental antitumor and toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, orgnas which are mainly affected, and to estimate its lethality in mice and rats given SKI 2053R through two routes of administration. In male and female rats given a single intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were over 3.00g/kg, respectively. In male and female mice given a signle intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were 2.44g/kg and 1.59g/kg, respectively, In a single intraperitoneal dose of SKI 2053R, we determined that $LD_{50}$ values of male and female rats were 227mg/kg and 182mg/kg, and those of male and female mice were 198mg/kg and 207mg/kg, respectively. In gross and histopathological examinations on dead animals, we found that kidney and liver were mainly affected.

• 한방안이비인후피부과학회지
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• 제27권1호
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• pp.68-78
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• 2014

Objectives : This study was carried out to evaluate the acute oral toxicity of Dictamnus dasycarpus Turcz in Sprague-Dawley(SD) rats. Methods : Male and female rats were administered orally with Dictamnus dasycarpus Turcz water extract of 1,000 mg/kg(low dosage group), 2,000 mg/kg(middle dosage group) and 4,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology. But we found out subtle changes in body weight and individual organ weight of the female group. In addition specific changes were observed in serum biochemical value of female group. Conclusions : These results suggest that water soluble extract of Dictamnus dasycarpus Turcz has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats. Also Dictamnus dasycarpus Turcz is expected to be sensitive with respect to the female.